OBJECTIVES: To assess the impact of brain metastasis (BrMets) on health care costs and survival among metastatic NSCLC patients in a geographically diverse commercially insured US population. METHODS: Retrospective analyses were conducted using a US commercial administrative claims database linking data from a lung cancer registry and mortality records from the Social Security Administration Death Master File (2005-2010). Two cohorts were formed – a) with BrMets, and b) without BrMets. Healthcare cost (hospitalization, ambulatory and pharmacy) and resource use (hospitalization, emergency {ER} and ambulatory visits) were compared using a generalized linear model (diagnosis →end of follow-up); a Cox proportional hazard model estimated impact on survival.  All models adjusted for stage at diagnosis, pre-diagnosis comorbidity, age, and gender. RESULTS: A total of 584 metastatic NSCLC patients were included (mean 60.5 years/56.3% male): 247 (42.3%) had claims-based evidence of BrMets and were more likely to have been diagnosed with stage IV disease (62.8% vs. 52.2% without BrMets). Overall survival was shorter among patients with evidence of BrMets (median = 13.5 vs. 17.0 months; HR=1.29, p<001); health plan enrollment duration was similar (median = 11.7 months). With similar lengths of follow-up, average health care costs following diagnosis of BrMets was 23% higher ($184,872 vs. $150,931; p=0.010) after adjustment for other factors.  The difference was consistent across resources: 25% higher hospitalization costs $46,871 vs. $37,504; p=.082); 23% higher ambulatory costs, ($121,224 vs. $98,276; p=0.033); 23% higher retail pharmacy costs, ($13,282 vs. $10,774; p=0.118).  Patients with BrMets averaged more hospitalizations (2.4 vs. 1.9; p=0.005), ER visits (2.7 vs. 2.2; p=0.067), and ambulatory encounters (111 vs. 92; p=0.005) from initial NSCLC diagnosis to end of follow-up. CONCLUSIONS: Intensity of resource use and costs were higher in metastatic NSCLC, especially in BrMets patients. Treatment that improves disease control could reduce the intensity of cost and resource use among NSCLC BrMets patients.